1. Field of the Invention
This invention relates to aerosol drug formulations. This invention also relates to dispersing aids for use in aerosol drug formulations. In another aspect this invention relates to aerosol formulations comprising hydrofluorocarbon propellants.
2. Description of the Related Art
Delivery of drugs to the lung by way of inhalation is an important means of treating a variety of conditions, including such common conditions as bronchial asthma and chronic obstructive pulmonary disease. Steroids, .beta.-2 agonists, and anti-cholinergic agents are among the drugs that are administered to the lung for such purposes. Such drugs are commonly administered to the lung in the form of an aerosol of particles of respirable size (less than about 10 .mu.m in diameter). In order to assure proper particle size in the aerosol, particles can be prepared in respirable size and then incorporated into a suspension formulation containing a propellant. Alternatively, formulations can be prepared in solution form in order to avoid the concern for proper particle size in the formulation. Solution formulations must nevertheless be dispensed in a manner that produces particles or droplets of respirable size.
Once prepared an aerosol formulation is filled into an aerosol canister equipped with a metered dose valve. In the hands of a patient the formulation is dispensed via an actuator adapted to direct the dose from the valve to the patient.
It is important that an aerosol formulation be stable such that the dose discharged from the metered dose valve is reproducible. Rapid creaming, settling, or flocculation after agitation are common sources of dose irreproducibility in suspension formulations. Sticking of the valve also can cause dose irreproducibility. In order to overcome these problems aerosol formulations often contain surfactants, which serve as suspending aids to stabilize the suspension for a time sufficient to allow for reproducible dosing. Certain surfactants also function as lubricants to lubricate the valve to assure smooth actuation. Myriad materials are known and disclosed for use as dispersing aids in aerosol formulations. Suitability of materials, however, is dependent on the particular drug and the propellant or class of propellant used in the formulation.
It is sometimes difficult to dissolve sufficient quantities of conventional surfactants in hydrofluorocarbon (HFC) propellants such as HFC-134a and HFC-227. Cosolvents have been used to overcome this problem. An alternative approach that avoids use of cosolvents involves materials that are soluble in hydrofluorocarbon propellants and are said to be effective surfactants or dispersing aids in an aerosol formulation. Among such materials are certain fluorinated surfactants and certain polyethoxy surfactants.
The materials used in medicinal aerosol formulations are taken into the lungs. It is therefore desirable that they be non-toxic or suitably metabolized or eliminated.